Administration of Anti-inflammatory M2 Macrophages Suppresses Progression of Angiotensin Ⅱ-Induced Aortic Aneurysm in Mice

Aortic aneurysm (AA) is a vascular disorder characterized pathologically by inflammatory cell invasion and extracellular matrix (ECM) degradation. It is known that regulation of the balance between pro-inflammatory M1 macrophages (M1Ms) and anti-inflammatory M2 macrophages (M2Ms) play a pivotal role in AA stabilization. We investigated the effects of M2M administration in an apolipoprotein E-deficient (apoE-/-) mouse model in which AA was induced by angiotensin Ⅱ (ATⅡ) infusion. Mice received intraperitoneal administration of 1 million M2Ms 4 weeks after ATII infusion. The M2Ms group exhibited reduced AA expansion, decreased expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein−1 (MCP)-1, decreased matrix metalloproteinase (MMP)-9 enzymatic activity, and a lower M1M/M2M ratio. Moreover, the M2M group exhibited upregulation of anti-inflammatory factors, including IL-4 and IL-10. PKH26-labeled M2Ms accounted for 6.5% of cells in the aneurysmal site and co-expressed CD206. Taken together, intraperitoneal administration of M2Ms inhibited AA expansion by reducing the inflammatory reaction via M2M dominance. This study shows that M2M administration might be useful for the treatment of AA.